Alexander disease type II

Summary

Alexander disease type II (MONDO:0018210) is a disease with 1 cohort gene.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 20

Clinical features

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0010873	Cervical spinal cord atrophy	Very frequent (80-99%)
HP:0011441	Abnormality of the medulla oblongata	Very frequent (80-99%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001251	Ataxia	Frequent (30-79%)
HP:0001257	Spasticity	Frequent (30-79%)
HP:0001260	Dysarthria	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0001618	Dysphonia	Frequent (30-79%)
HP:0002015	Dysphagia	Frequent (30-79%)
HP:0002313	Spastic paraparesis	Frequent (30-79%)
HP:0002518	Abnormal periventricular white matter morphology	Frequent (30-79%)
HP:0002839	Urinary bladder sphincter dysfunction	Frequent (30-79%)
HP:0003487	Babinski sign	Frequent (30-79%)
HP:0003690	Limb muscle weakness	Frequent (30-79%)
HP:0007109	Periventricular cysts	Frequent (30-79%)
HP:0010530	Palatal myoclonus	Frequent (30-79%)
HP:0012332	Abnormal autonomic nervous system physiology	Frequent (30-79%)
HP:0002063	Rigidity	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Alexander disease type II
Mondo ID	MONDO:0018210
Orphanet	363722
UMLS	C5679914
MedGen	1842714
GARD	0017573
Is cancer (heuristic)	no

Also known as: AxD type II

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › leukodystrophy › Alexander disease › Alexander disease type II

Related subtypes (1): Alexander disease type I

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GFAP	Definitive	Autosomal dominant	Alexander disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GFAP	Orphanet:363717	Alexander disease type I
GFAP	Orphanet:363722	Alexander disease type II

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GFAP	HGNC:4235	ENSG00000131095	P14136	Glial fibrillary acidic protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GFAP	Glial fibrillary acidic protein	GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GFAP	Other/Unknown	no		Intermed_filament_DNA-bd, IF_conserved, IF_rod_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
dorsal motor nucleus of vagus nerve	1
inferior olivary complex	1
medulla oblongata	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GFAP	210	broad	marker	medulla oblongata, inferior olivary complex, dorsal motor nucleus of vagus nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GFAP	6,997

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GFAP	P14136	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chaperone Mediated Autophagy	1	496.5×	0.003	GFAP
Nuclear signaling by ERBB4	1	346.1×	0.003	GFAP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of Schwann cell proliferation	1	16852.0×	8e-04	GFAP
Schwann cell proliferation	1	5617.3×	8e-04	GFAP
regulation of neurotransmitter uptake	1	5617.3×	8e-04	GFAP
neuron projection regeneration	1	4213.0×	8e-04	GFAP
D-aspartate import across plasma membrane	1	3370.4×	8e-04	GFAP
regulation of chaperone-mediated autophagy	1	3370.4×	8e-04	GFAP
Bergmann glial cell differentiation	1	1532.0×	0.002	GFAP
astrocyte development	1	1123.5×	0.002	GFAP
enteric nervous system development	1	991.3×	0.002	GFAP
regulation of protein-containing complex assembly	1	732.7×	0.002	GFAP
neural crest cell migration	1	337.0×	0.005	GFAP
long-term synaptic potentiation	1	280.9×	0.005	GFAP
intermediate filament organization	1	240.7×	0.005	GFAP
negative regulation of neuron projection development	1	237.3×	0.005	GFAP
extracellular matrix organization	1	122.1×	0.009	GFAP
gene expression	1	79.9×	0.013	GFAP
intracellular protein transport	1	64.8×	0.015	GFAP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GFAP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GFAP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GFAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.